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1.
Artículo en Inglés | MEDLINE | ID: mdl-39033545

RESUMEN

In situ 3D printing is attractive for the direct repair of bone defects in underdeveloped countries and in emergency situations. So far, the lack of an interesting method to produce filament using FDA-approved biopolymers and nanoceramics combined with a portable strategy limits the use of in situ 3D printing. Herein, we investigated the osseointegration of new nanocomposite filaments based on polylactic acid (PLA), laponite (Lap), and hydroxyapatite (Hap) printed directly at the site of the bone defect in rats using a portable 3D printer. The filaments were produced using a single-screw extruder (L/D = 26), without the addition of solvents that can promote the toxicity of the materials. In vitro performance was evaluated in the cell differentiation process with mesenchymal stem cells (MSC) by an alkaline phosphatase activity test and visualization of mineralization nodules; a cell viability test and total protein dosage were performed to evaluate cytotoxicity. For the in vivo analysis, the PLA/Lap composite filaments with a diameter of 1.75 mm were printed directly into bone defects of Wistar rats using a commercially available portable 3D printer. Based on the in vitro and in vivo results, the in situ 3D printing technique followed by rapid cooling proved to be promising for bone tissue engineering. The absence of fibrous encapsulation and inflammatory processes became a good indicator of effectiveness in terms of biocompatibility parameters and bone tissue formation, and the use of the portable 3D printer showed a significant advantage in the application of this material by in situ printing.

2.
Int J Nanomedicine ; 19: 2655-2673, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38500680

RESUMEN

Introduction: Immunotherapy has revolutionized cancer treatment by harnessing the immune system to enhance antitumor responses while minimizing off-target effects. Among the promising cancer-specific therapies, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted significant attention. Methods: Here, we developed an ionizable lipid nanoparticle (LNP) platform to deliver TRAIL mRNA (LNP-TRAIL) directly to the tumor microenvironment (TME) to induce tumor cell death. Our LNP-TRAIL was formulated via microfluidic mixing and the induction of tumor cell death was assessed in vitro. Next, we investigated the ability of LNP-TRAIL to inhibit colon cancer progression in vivo in combination with a TME normalization approach using Losartan (Los) or angiotensin 1-7 (Ang(1-7)) to reduce vascular compression and deposition of extracellular matrix in mice. Results: Our results demonstrated that LNP-TRAIL induced tumor cell death in vitro and effectively inhibited colon cancer progression in vivo, particularly when combined with TME normalization induced by treatment Los or Ang(1-7). In addition, potent tumor cell death as well as enhanced apoptosis and necrosis was found in the tumor tissue of a group treated with LNP-TRAIL combined with TME normalization. Discussion: Together, our data demonstrate the potential of the LNP to deliver TRAIL mRNA to the TME and to induce tumor cell death, especially when combined with TME normalization. Therefore, these findings provide important insights for the development of novel therapeutic strategies for the immunotherapy of solid tumors.


Asunto(s)
Neoplasias del Colon , Liposomas , Nanopartículas , Microambiente Tumoral , Animales , Ratones , Ligandos , Apoptosis , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Factor de Necrosis Tumoral alfa , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo
4.
Int J Nanomedicine ; 18: 6153-6183, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37915750

RESUMEN

Carbon-based nanomaterials (CBNs) are a category of nanomaterials with various systems based on combinations of sp2 and sp3 hybridized carbon bonds, morphologies, and functional groups. CBNs can exhibit distinguished properties such as high mechanical strength, chemical stability, high electrical conductivity, and biocompatibility. These desirable physicochemical properties have triggered their uses in many fields, including biomedical applications. In this review, we specifically focus on applying CBNs as scaffolds in tissue engineering, a therapeutic approach whereby CBNs can act for the regeneration or replacement of damaged tissue. Here, an overview of the structures and properties of different CBNs will first be provided. We will then discuss state-of-the-art advancements of CBNs and hydrogels as scaffolds for regenerating various types of human tissues. Finally, a perspective of future potentials and challenges in this field will be presented. Since this is a very rapidly growing field, we expect that this review will promote interdisciplinary efforts in developing effective tissue regeneration scaffolds for clinical applications.


Asunto(s)
Nanoestructuras , Ingeniería de Tejidos , Humanos , Hidrogeles/química , Carbono , Andamios del Tejido/química
5.
Int J Nanomedicine ; 18: 5891-5904, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37873551

RESUMEN

Introduction: Chimeric antigen receptor (CAR) cell therapy represents a hallmark in cancer immunotherapy, with significant clinical results in the treatment of hematological tumors. However, current approved methods to engineer T cells to express CAR use viral vectors, which are integrative and have been associated with severe adverse effects due to constitutive expression of CAR. In this context, non-viral vectors such as ionizable lipid nanoparticles (LNPs) arise as an alternative to engineer CAR T cells with transient expression of CAR. Methods: Here, we formulated a mini-library of LNPs to deliver pDNA to T cells by varying the molar ratios of excipient lipids in each formulation. LNPs were characterized and screened in vitro using a T cell line (Jurkat). The optimized formulation was used ex vivo to engineer T cells derived from human peripheral blood mononuclear cells (PBMCs) for the expression of an anti-CD19 CAR (CAR-CD19BBz). The effectiveness of these CAR T cells was assessed in vitro against Raji (CD19+) cells. Results: LNPs formulated with different molar ratios of excipient lipids efficiently delivered pDNA to Jurkat cells with low cytotoxicity compared to conventional transfection methods, such as electroporation and lipofectamine. We show that CAR-CD19BBz expression in T cells was transient after transfection with LNPs. Jurkat cells transfected with our top-performing LNPs underwent activation when exposed to CD19+ target cells. Using our top-performing LNP-9-CAR, we were able to engineer human primary T cells to express CAR-CD19BBz, which elicited significant specific killing of CD19+ target cells in vitro. Conclusion: Collectively, our results show that LNP-mediated delivery of pDNA is a suitable method to engineer human T cells to express CAR, which holds promise for improving the production methods and broader application of this therapy in the future.


Asunto(s)
Excipientes , Nanopartículas , Humanos , Leucocitos Mononucleares , Plásmidos/genética , ADN/genética , Lípidos
6.
J Funct Biomater ; 14(9)2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37754851

RESUMEN

The use of bioactive materials, such as Ximenia americana L., to stimulate the bone repair process has already been studied; however, the synergistic effects of its association with light emitting diode (LED) have not been reported. The present work aims to evaluate the effect of its stem bark extract incorporated into methacrylate gelatin hydrogel (GelMA) on the bone repair process using pure hydrogel and hydrogel associated with LED therapy. For this purpose, the GelMA hydrogel loaded with Ximenia americana L. extract (steam bark) was produced, characterized and applied in animal experiments. The tests were performed using 50 male Wistar rats (divided into 5 groups) submitted to an induced tibia diaphyseal fracture. The therapy effects were verified for a period of 15 and 30 days of treatment using histological analysis and Raman spectroscopy. After 15 days of induced lesion/treatment, the new bone formation was significantly higher in the GXG (GelMA + X. americana L.) group compared to the control group (p < 0.0001). After 30 days, a statistically significant difference was observed when comparing the GXLEDG (GelMA + X. americana L. + LED) and the control group (p < 0.0001), the GXG and the control group (p < 0.001), and when comparing the GG, GXG (p < 0.005) and GXLEDG (p < 0.001) groups. The results shows that the Ximenia americana L. stem extract incorporated into GelMA hydrogel associated with LED therapy is a potentiator for animal bone repair.

7.
iScience ; 26(2): 106039, 2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36761021

RESUMEN

Three-dimensional (3D) bioprinting has emerged as a class of promising techniques in biomedical research for a wide range of related applications. Specifically, stereolithography apparatus (SLA) and digital light processing (DLP)-based vat-polymerization techniques are highly effective methods of bioprinting, which can be used to produce high-resolution and architecturally sophisticated structures. Our review aims to provide an overview of SLA- and DLP-based 3D bioprinting strategies, starting from factors that affect these bioprinting processes. In addition, we summarize the advances in bioinks used in SLA and DLP, including naturally derived and synthetic bioinks. Finally, the biomedical applications of both SLA- and DLP-based bioprinting are discussed, primarily centered on regenerative medicine and tissue modeling engineering.

8.
Mol Aspects Med ; 91: 101108, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-35987701

RESUMEN

The field of precision medicine allows for tailor-made treatments specific to a patient and thereby improve the efficiency and accuracy of disease prevention, diagnosis, and treatment and at the same time would reduce the cost, redundant treatment, and side effects of current treatments. Here, the combination of organ-on-a-chip and bioprinting into engineering high-content in vitro tissue models is envisioned to address some precision medicine challenges. This strategy could be employed to tackle the current coronavirus disease 2019 (COVID-19), which has made a significant impact and paradigm shift in our society. Nevertheless, despite that vaccines against COVID-19 have been successfully developed and vaccination programs are already being deployed worldwide, it will likely require some time before it is available to everyone. Furthermore, there are still some uncertainties and lack of a full understanding of the virus as demonstrated in the high number new mutations arising worldwide and reinfections of already vaccinated individuals. To this end, efficient diagnostic tools and treatments are still urgently needed. In this context, the convergence of bioprinting and organ-on-a-chip technologies, either used alone or in combination, could possibly function as a prominent tool in addressing the current pandemic. This could enable facile advances of important tools, diagnostics, and better physiologically representative in vitro models specific to individuals allowing for faster and more accurate screening of therapeutics evaluating their efficacy and toxicity. This review will cover such technological advances and highlight what is needed for the field to mature for tackling the various needs for current and future pandemics as well as their relevancy towards precision medicine.


Asunto(s)
COVID-19 , Humanos , Vacunas contra la COVID-19 , SARS-CoV-2 , Medicina de Precisión
9.
J Funct Biomater ; 13(4)2022 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-36412893

RESUMEN

Three-dimensional bioprinting is a powerful technique for manufacturing improved engineered tissues. Three-dimensional bioprinted hydrogels have significantly advanced the medical field to repair cartilage tissue, allowing for such constructs to be loaded with different components, such as cells, nanoparticles, and/or drugs. Cartilage, as an avascular tissue, presents extreme difficulty in self-repair when it has been damaged. In this way, hydrogels with optimal chemical and physical properties have been researched to respond to external stimuli and release various bioactive agents to further promote a desired tissue response. For instance, methacryloyl gelatin (GelMA) is a type of modified hydrogel that allows for the encapsulation of cells, as well as oxygen-releasing nanoparticles that, in the presence of an aqueous medium and through controlled porosity and swelling, allow for internal and external environmental exchanges. This review explores the 3D bioprinting of hydrogels, with a particular focus on GelMA hydrogels, to repair cartilage tissue. Recent advances and future perspectives are described.

10.
Polymers (Basel) ; 14(20)2022 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-36297865

RESUMEN

In this work, Coca-Cola® bottles were reused as a PET polymer (rPET) source to produce electrospun polymeric nanofibers. The nanofibers were electrospun from polymer solutions with different concentrations of reduced graphene oxide (rGO) incorporated for applications in somatosensory electrical stimulation. The rPET/rGO nanofiber mats were characterized by SEM, TEM, Raman, DSC, TGA, and DMA and the results showed that the incorporation of rGO in electrospun rPET fibers produced rPET/rGO composites. The rPET/rGO composites were then evaluated for possible application as dry electrodes. Moreover, with a preliminary test of numerous volunteers, the rPET/rGO dry electrode showed promising results. The rPET/rGO electrodes showed good performance and applicability to make dry electrodes, and these have applications as dry or wearable electrodes to produce electrochemical sensors.

11.
Artículo en Inglés | MEDLINE | ID: mdl-35932519

RESUMEN

Accidents involving spiders from the genus Loxosceles cause medical emergencies in several countries of South America. The species Loxosceles laeta is ubiquitously present in Peru and is responsible for severe accidents in this country. To further characterize L. laeta venom components and to unveil possible variations in the Peruvian population, we provide an overview of the toxins-related transcripts present in the venom gland of Peruvian L. laeta. A dataset from a cDNA library previously sequenced by MiSeq sequencer (Illumina) was re-analyzed and the obtained data was compared with available sequences from Loxosceles toxins. Phospholipase-D represent the majority (69,28 %) of the transcripts related to venom toxins, followed by metalloproteases (20,72 %), sicaritoxins (6,03 %), serine-proteases (2,28 %), hyaluronidases (1,80 %) and Translationally Controlled Tumor Protein (TCTP) (0,56 %). New sequences of phospholipases D,sicaritoxins, hyaluronidase, TCTP and serine proteinases were described. Differences between the here-described toxin sequences and others, previously identified in venom glands from other spiders, were visualized upon sequence alignments. In addition, an in vitro hyaluronidase activity assay was also performed to complement comparisons between Peruvian and Brazilian L. laeta venom enzymatic activities, revealing a superior activity in the venom from Brazilian specimens. These new data provide a molecular basis that can help to explain the difference in toxicity among L. laeta venoms from different countries in South America.


Asunto(s)
Hialuronoglucosaminidasa , Venenos de Araña , Animales , Biblioteca de Genes , Hialuronoglucosaminidasa/genética , Perú , Alineación de Secuencia , Venenos de Araña/genética
12.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-22278277

RESUMEN

Rapid antigen tests play an important role in the monitoring and mitigation of the COVID-19 pandemic, as it provides an easy, fast and efficient diagnosis with minimum infrastructure requirements. However, as new variants of concern continue to emerge, mutations in the virus genome may impair the recognition of the mutated antigen by the tests. Therefore, it is essential to re-assess the tests sensitivity as the virus mutation profile undergoes significant changes. Here, we prospectively accessed the performance of the DPP(R) SARS-CoV-2 Antigen test in the context of an omicron-dominant real-life setting. We evaluated 347 unselected individuals (all-comers) from a public testing center in Brazil, performing the rapid antigen test diagnosis at point-of-care with fresh samples. The combinatory result from two distinct RT-qPCR methods was employed as reference and 13 samples with discordant PCR results were excluded. The assessment of the rapid test in 67 PCR-positive and 265 negative samples revealed an overall sensitivity of 80.5%, specificity of 99.2% and positive/negative predictive values higher than 95%. However, we observed that the sensitivity was dependent on the viral load (sensitivity in Ct<31 = 93.7%; Ct>31 = 47.4%). Furthermore, we were able to confirm that the positive samples evaluated in the study were Omicron (BA.1/BA.1.1) by whole-genome sequencing (n=40) and multiplex RT-qPCR (n=17). Altogether, the data obtained from a real-life prospective cohort supports that the rapid antigen test sensitivity for the Omicron remains high and underscores the reliability of the test for COVID-19 diagnosis in a setting with high disease prevalence and limited PCR testing capability.

13.
J Fungi (Basel) ; 8(4)2022 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-35448604

RESUMEN

The rubber tree, Hevea brasiliensis, is a neotropical Amazonian species. Despite its high economic value and fungi associated with native individuals, in its original area in Brazil, it has been scarcely investigated and only using culture-dependent methods. Herein, we integrated in silico approaches with novel field/experimental approaches and a case study of shotgun metagenomics and small RNA metatranscriptomics of an adult individual. Scientific literature, host fungus, and DNA databases are biased to fungal taxa, and are mainly related to rubber tree diseases and in non-native ecosystems. Metabarcoding retrieved specific phyllospheric core fungal communities of all individuals, adults, plantlets, and leaves of the same plant, unravelling hierarchical structured core mycobiomes. Basidiomycotan yeast-like fungi that display the potential to produce antifungal compounds and a complex of non-invasive ectophytic parasites (Sooty Blotch and Flyspeck fungi) co-occurred in all samples, encompassing the strictest core mycobiome. The case study of the same adult tree (previously studied using culture-dependent approach) analyzed by amplicon, shotgun metagenomics, and small RNA transcriptomics revealed a high relative abundance of insect parasite-pathogens, anaerobic fungi and a high expression of Trichoderma (a fungal genus long reported as dominant in healthy wild rubber trees), respectively. Altogether, our study unravels new and intriguing information/hypotheses of the foliar mycobiome of native H. brasiliensis, which may also occur in other native Amazonian trees.

14.
Int J Nanomedicine ; 17: 1111-1124, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35309966

RESUMEN

Introduction: Three of the main requirements that remain major challenges in tissue engineering of the knee meniscus are to engineer scaffolds with compatible anatomical shape, good mechanical properties, and microstructure able to mimic the architecture of the extracellular matrix (ECM). In this context, we presented a new biofabrication strategy to develop a three-dimensional (3D) meniscus-regenerative scaffold with custom-made macroscopic size and microarchitecture bioinspired by the organization of structural fibers of native tissue ECM. Methods: The concept was based on the combination of bioprinted cell-laden hydrogel (type 1 collagen) reinforced by multilayers of biomimetically aligned electrospun nanofibrous mats (polycaprolactone/carbon nanotubes, PCL/CNT), using a patient-specific 3D digital meniscus model reconstructed from MRI data by free and open-source software. Results: The results showed that the incorporation of aligned nanofibers sheets between the hydrogel layers enhanced the scaffold's structural integrity and shape fidelity compared to the nanofiber-free collagen hydrogel. Furthermore, mechanical compression tests demonstrated that the presence of nanofiber layers significantly improved the mechanical properties of the bioprinted construct. Importantly, the introduction of PCL/CNT nanofibrous mats between the layers of the bioprinted collagen hydrogel did not negatively affect cell viability, in which mesenchymal stem cells remained viable even after 7 days of culture within the scaffold. Conclusion: Overall, these findings evidence that this bioengineering approach offers a promising strategy for fabricating biomimetic meniscus scaffolds for tissue engineering.


Asunto(s)
Menisco , Nanofibras , Nanotubos de Carbono , Humanos , Nanofibras/química , Ingeniería de Tejidos/métodos , Andamios del Tejido/química
15.
Bioengineering (Basel) ; 8(11)2021 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-34821717

RESUMEN

Nanocomposite scaffolds based on the combination of polymeric nanofibers with nanohydroxyapatite are a promising approach within tissue engineering. With this strategy, it is possible to synthesize nanobiomaterials that combine the well-known benefits and advantages of polymer-based nanofibers with the osteointegrative, osteoinductive, and osteoconductive properties of nanohydroxyapatite, generating scaffolds with great potential for applications in regenerative medicine, especially as support for bone growth and regeneration. However, as efficiently incorporating nanohydroxyapatite into polymeric nanofibers is still a challenge, new methodologies have emerged for this purpose, such as electrodeposition, a fast, low-cost, adjustable, and reproducible technique capable of depositing coatings of nanohydroxyapatite on the outside of fibers, to improve scaffold bioactivity and cell-biomaterial interactions. In this short review paper, we provide an overview of the electrodeposition method, as well as a detailed discussion about the process of electrodepositing nanohydroxyapatite on the surface of polymer electrospun nanofibers. In addition, we present the main findings of the recent applications of polymeric micro/nanofibrous scaffolds coated with electrodeposited nanohydroxyapatite in tissue engineering. In conclusion, comments are provided about the future direction of nanohydroxyapatite electrodeposition onto polymeric nanofibers.

16.
J Funct Biomater ; 12(2)2021 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-34200191

RESUMEN

BACKGROUND: Several studies proved that anodic oxidation improves osseointegration. This study aimed to optimize osseointegration through anodization in dental implants, obtaining anatase phase and controlled nanotopography. METHODS: The division of the groups with 60 titanium implants was: control (CG); sandblasted (SG); anodized (AG): anodized pulsed current (duty cycle 30%, 30 V, 0.2 A and 1000 Hz). Before surgery, surface characterization was performed using Atomic Force Microscopy (AFM), Scanning Electron Microscopy (SEM), X-ray Dispersive Energy Spectroscopy (EDS) and Raman Spectroscopy. For in vivo tests, 10 New Zealand white rabbits received an implant from each group. The sacrifice period was 2 and 6 weeks (n = 5) and the specimens were subjected to computed microtomography (µCT) and reverse torque test. RESULTS: AFM and SEM demonstrated a particular nanotopography on the surface in AG; the anatase phase was proved by Raman spectroscopy. In the µCT and in the reverse torque test, the AG group presented better results than the other groups. CONCLUSION: The chemical composition and structure of the TiO2 film were positively affected by the anodizing technique, intensifying the biological characteristics in osseointegration.

17.
J Funct Biomater ; 12(2)2021 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-34063270

RESUMEN

Different strategies have been employed to provide adequate nutrients for engineered living tissues. These have mainly revolved around providing oxygen to alleviate the effects of chronic hypoxia or anoxia that result in necrosis or weak neovascularization, leading to failure of artificial tissue implants and hence poor clinical outcome. While different biomaterials have been used as oxygen generators for in vitro as well as in vivo applications, certain problems have hampered their wide application. Among these are the generation and the rate at which oxygen is produced together with the production of the reaction intermediates in the form of reactive oxygen species (ROS). Both these factors can be detrimental for cell survival and can severely affect the outcome of such studies. Here we present calcium peroxide (CPO) encapsulated in polycaprolactone as oxygen releasing microparticles (OMPs). While CPO releases oxygen upon hydrolysis, PCL encapsulation ensures that hydrolysis takes place slowly, thereby sustaining prolonged release of oxygen without the stress the bulk release can endow on the encapsulated cells. We used gelatin methacryloyl (GelMA) hydrogels containing these OMPs to stimulate survival and proliferation of encapsulated skeletal myoblasts and optimized the OMP concentration for sustained oxygen delivery over more than a week. The oxygen releasing and delivery platform described in this study opens up opportunities for cell-based therapeutic approaches to treat diseases resulting from ischemic conditions and enhance survival of implants under severe hypoxic conditions for successful clinical translation.

18.
Int J Nanomedicine ; 16: 667-682, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33531806

RESUMEN

BACKGROUND: Nanostructured surface modifications of Ti-based biomaterials are moving up from a highly-promising to a successfully-implemented approach to developing safe and reliable implants. METHODS: The study's main objective is to help consolidate the knowledge and identify the more suitable experimental strategies related to TiO2 nanotubes-modified surfaces. In this sense, it proposes the thorough investigation of two optimized nanotubes morphologies in terms of their biological activity (cell cytotoxicity, alkaline phosphatase activity, alizarin red mineralization test, and cellular adhesion) and their electrochemical behavior in simulated body fluid (SBF) electrolyte. Layers of small-short and large-long nanotubes were prepared and investigated in their amorphous and crystallized states and compared to non-anodized samples. RESULTS: Results show that much more than the surface area development associated with the nanotubes' growth; it is the heat treatment-induced change from amorphous to crystalline anatase-rutile structures that ensure enhanced biological activity coupled to high corrosion resistance. CONCLUSION: Compared to both non-anodized and amorphous nanotubes layers, the crystallized nano-structures' outstanding bioactivity was related to the remarkable increase in their hydrophilic behavior, while the enhanced electrochemical stability was ascribed to the thickening of the dense rutile barrier layer at the Ti surface beneath the nanotubes.


Asunto(s)
Nanotubos/química , Prótesis e Implantes , Titanio/química , Fosfatasa Alcalina/metabolismo , Adhesión Celular , Línea Celular Tumoral , Supervivencia Celular , Corrosión , Electroquímica , Electrólitos/química , Humanos , Nanotubos/ultraestructura , Humectabilidad
19.
Mater Sci Eng C Mater Biol Appl ; 120: 111776, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33545906

RESUMEN

A biomineralization processes is disclosed for engineering nanomaterials that support bone repair. The material was fabricated through a hot press process using electrospun poly(lactic acid) (PLA) matrix covered with hybrid composites of carbon nanotubes/graphene nanoribbons (GNR) and nanohydroxyapatite (nHA). Various scaffolds were devised [nHA/PLA, PLA/GNR, and PLA/nHA/GNR (1 and 3%)] and their structure and morphology characterized through Scanning electron microscopy (SEM), Energy dispersive X-ray spectroscopy (EDS), and Atomic force microscope (AFM). Moreover, thorough biocompatibility and toxicity studies were performed. Here, in vivo studies on toxicity and cytotoxicity were conducted in aqueous dispersions of the biomaterials at concentrations of 30, 60, and 120 µg/mL using the Allium cepa test. Further toxicity studies were performed through hemolysis toxicity tests and genotoxicity tests evaluating the damage index and damage frequencies of DNAs through comet assays with samples of the animals' peripheral blood, marrow, and liver. Additionally, the regenerative activity of the scaffolds was analyzed by measuring the cortical tibiae of rats oophorectomized implanted with the biomaterials. Biochemical analyzes [glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), urea, calcium, phosphorus, and alkaline phosphatase (ALP)] were also performed on blood samples. The results suggested a toxicity and cytotoxicity level for the GNR biomaterials at a concentration of 60 and 120 µg/mL, but non-toxicity and cytotoxicity for the 30 µg/mL concentration. The scaffolds obtained at a concentration of 0.3 mg/cm2 were not toxic in the hemolysis test and demonstrated no cytotoxicity, genotoxicity, and mutagenicity in the blood, marrow, and liver analyzes of the animals, corroborating data from the biochemical markers of GPT, GOT, and urea. Tissue regeneration was performed in all groups and was more pronounced in the group containing the combination of nHA/GNR (3%), which is consistent with the data obtained for the calcium, serum phosphorus, and ALP concentrations. Consequently, the study indicates that the engineered nanobiomaterial is a promising candidate for bone tissue repair and regenerative applications. STATEMENT OF SIGNIFICANCE: The scientific contribution of this study is the engineering of a synthetic hybrid biomaterial, in nanoscale by a pressing and heating process. A biodegradable polymeric matrix was covered on both sides with a carbonated hybrid bioceramic/graphene nanoribbons (GNR), which has hydrophilic characteristics, with chemical elements stoichiometrically similar to bone mineral composition. The nanomaterial displayed promising bone regeneration ability, which is the first example to be used in an osteoporotic animal model. Moreover, detailed biocompatibility and toxicity studies were performed on the nanomaterials and their compositions, which is of great interest for the scientific community.


Asunto(s)
Durapatita , Nanotubos de Carbono , Animales , Biomineralización , Regeneración Ósea , Ratas , Ingeniería de Tejidos , Andamios del Tejido
20.
J Funct Biomater ; 12(1)2021 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-33562592

RESUMEN

Electrospun ultrathin fibrous scaffold filed with synthetic nanohydroxyapatite (nHAp) and graphene nanoribbons (GNR) has bioactive and osteoconductive properties and is a plausible strategy to improve bone regeneration. Poly(butylene-adipate-co-terephthalate) (PBAT) has been studied as fibrous scaffolds due to its low crystallinity, faster biodegradability, and good mechanical properties; however, its potential for in vivo applications remains underexplored. We proposed the application of electrospun PBAT with high contents of incorporated nHAp and nHAp/GNR nanoparticles as bone grafts. Ultrathin PBAT, PBAT/nHAp, and PBAT/nHAp/GNR fibers were produced using an electrospinning apparatus. The produced fibers were characterized morphologically and structurally using scanning electron (SEM) and high-resolution transmission electron (TEM) microscopies, respectively. Mechanical properties were analyzed using a texturometer. All scaffolds were implanted into critical tibia defects in rats and analyzed after two weeks using radiography, microcomputed tomography, histological, histomorphometric, and biomechanical analyses. The results showed through SEM and high-resolution TEM characterized the average diameters of the fibers (ranged from 0.208 µm ± 0.035 to 0.388 µm ± 0.087) and nHAp (crystallite around 0.28, 0.34, and 0.69 nm) and nHAp/GNR (200-300 nm) nanoparticles distribution into PBAT matrices. Ultrathin fibers were obtained, and the incorporated nHAp and nHAp/GNR nanoparticles were well distributed into PBAT matrices. The addition of nHAp and nHAp/GNR nanoparticles improved the elastic modulus of the ultrathin fibers compared to neat PBAT. High loads of nHAp/GNR (PBATnH5G group) improved the in vivo lamellar bone formation promoting greater radiographic density, trabecular number and stiffness in the defect area 2 weeks after implantation than control and PBAT groups.

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